Reduction of colonic inflammation in HLA-B27 transgenic rats by feeding Marie Ménard apples, rich in polyphenols

Inflammatory bowel diseases (IBD) are immunomediated ailments affecting millions of individuals. Although diet is regarded as an important factor influencing IBD, there are no accepted dietary recommendations presently available. We administered 7.6 % lyophilised apples obtained from two cultivars (Golden Delicious and Marie Ménard, low and high in polyphenols, respectively) to HLA-B27 transgenic rats which develop spontaneous IBD. After 3 months feeding, rats fed Marie Ménard apples had reduced myeloperoxidase activity (3.6 (sem 0.3) v. 2.2 (sem 0.2) U/g tissue; P <0.05) and reduced cyclo-oxygenase-2 (P <0.05) and inducible NO synthase gene expression (P <0.01) in the colon mucosa and significantly less diarrhoea (P <0.05), compared with control rats. Cell proliferation in the colon mucosa was reduced significantly by feeding Golden Delicious apples, with a borderline effect of Marie Ménard apples. Gene expression profiling of the colon mucosa, analysed using the Whole Rat Genome 4 x 44 K Agilent Arrays, revealed a down-regulation of the pathways of PG synthesis, mitogen-activated protein kinase (MAPK) signalling and TNFalpha-NF-kappaB in Marie Ménard-fed rats. In the stools of the animals of this group we also measured a significant reduction of bacteria of the Bacteriodes fragilis group. In conclusion, the administration of Marie Ménard apples, rich in polyphenols and used at present only in the manufacturing of cider, ameliorates colon inflammation in transgenic rats developing spontaneous intestinal inflammation, suggesting the possible use of these and other apple varieties to control inflammation in IBD patient

The Potamophylax nigricornis group (Trichoptera, Limnephilidae): resolution of phylogenetic species by fine structure analysis

Applying the phylogenetic species concept and the sexual selection theory we have reviewed some natal aspects of incipient species and their accelerated evolution. How can we recognise early stages of divergence? Which selection pressures are at work during speciation? Which pathways accelerate the speed of speciation? Which kinds of trait variabilities makes difficult to find initial split criteria? Elaborating the principles of Fine Structure Analysis (FSA) and the morphological Initial Split Criteria (ISP) it was discovered that the European spring dwelling caddisfly Potamophylax nigricornis doesn’tbelong to a single species. It represents an entire species group with seventeen peripatric species evolving on the southernperipheries of the distributional area. Four new species subgroups have been erected: Potamophylax nigricornis new species subgroup, P. elegantulus new species subgroup, P. horgos new species subgroup, P. simas new species subgroup. Eleven new species have been described: Potamophylax apados sp. nov., P. fules sp. nov., P. fureses sp. nov., P. hasas sp. novov., P. horgos sp. nov., P. kethas sp. nov., P. lemezes sp. nov., P. peremes sp. nov., P. simas sp. nov., P. tuskes sp. nov., P. ureges sp. nov. One Potamophylax sp. nov. has been differentiated and three new species status have been documented:Potamophylax elegantulus (Klapálek) stat. n., P. mista (Navás) stat. nov., P. testaceus (Zetterstedt) stat. nov

Hydrochlorothiazide Use and Risk of Nonmelanoma Skin Cancers: A Biological Plausibility Study

Recent studies reported the association between increased risk of nonmelanoma skin cancers (NMSCs) and the use of hydrochlorothiazide (HCTZ), one of the most commonly prescribed diuretic, antihypertensive drug, over the world. Although HCTZ is known to be photosensitizing, the mechanisms involved in its potential prophotocarcinogenic effects remain unclear. Under acute exposure, therapeutically relevant concentrations of HCTZ (70, 140, and 370 ng/mL) amplified UVA-induced double-strand breaks, oxidative DNA, and protein damage in HaCaT human keratinocytes, and this effect was associated to a defective activity of the DNA repair enzyme, OGG1. Oxidative damage to DNA, but not that to proteins, was reversible within few hours. After chronic, combined exposure to HCTZ (70 ng/mL) and UVA (10 J/cm(2)), for 9 weeks, keratinocytes acquired a dysplastic-like phenotype characterized by a multilayered morphology and alterations in cell size, shape, and contacts. At the ultrastructural level, several atypical and enlarged nuclei and evident nucleoli were also observed. These transformed keratinocytes were apoptosis resistant, exhibited enhanced clonogenicity capacity, increased DNA damage and inflammation, defective DNA repair ability, and increased expression of the oncogene ΔNp63α and intranuclear β-catenin accumulation (a hallmark of Wnt pathway activation), compared to those treated with UVA alone. None of these molecular, morphological, or functional effects were observed in cells treated with HCTZ alone. All these features resemble in part those of preneoplastic lesions and NMSCs and provide evidence of a biological plausibility for the association among exposure to UVA, use of HCTZ, and increased risk of NMSCs. These results are of translational relevance since we used environmentally relevant UVA doses and tested HCTZ at concentrations that reflect the plasma levels of doses used in clinical practice. This study also highlights that drug safety data should be followed by experimental evaluations to clarify the mechanistic aspects of adverse events

Analysis of oxidative stress-related markers in Crohn&#8217;s disease patients at surgery and correlations with clinical findings

Crohn&rsquo; disease (CD) patients are at high risk of postoperative recurrence and new tools for the assessment of disease activity are needed to prevent long-term complications. In these patients, the over-production of ROS generated by inflamed bowel tissue and inflammatory cells activates a pathogenic cascade that further exacerbates inflammation and leads to increased oxidative damage to DNA, proteins, and lipids. We measured the products of protein/lipid oxidation and the total antioxidant capacity (ferric reducing ability of plasma, FRAP) in the serum of CD patients with severe disease activity requiring surgery with the aim to characterize their redox status and identify associations between oxidative stress-related markers and their clinical characteristics. At the systemic level, CD was associated with increased levels of protein and lipid oxidation products when compared to healthy volunteers, even though the FRAP values were similar. Advanced oxidation protein product (AOPP) levels showed the highest difference between patients and the controls (11.25, 5.02&ndash;15.15, vs. 1.36, 0.75&ndash;2.70, median, interquartile range; p &lt; 0.0001) and the analysis of receiver operating characteristic (ROC) curves, indicated for AOPP, the best area under the curve (AUC) value for CD prediction. Advanced glycated end-products (AGEs) were also significantly higher in CD patients (p &lt; 0.01), which is of interest since AOPP and AGEs are both able to activate the membrane receptor for advanced glycation end products (RAGE) involved in inflammatory diseases. Thiobarbituric acid reactive substance (TBARS) levels were significantly higher in CD patients with ileal localization and aggressive disease behavior, in smokers, and in patients suffering from allergies. In conclusion, our data indicate that circulating oxidative stress biomarkers may be attractive candidates as disease predictors as well as for clinical or therapeutic monitoring of CD. Our results also suggest that AOPP/AGEs and RAGE signaling may represent a pathogenic factor and a potential therapeutic target in CD

In need of mediation: The relation between syntax and information structure

This paper defends the view that syntax does not directly interact with information structure. Rather, information structure affects prosody, and only the latter has an interface with syntax. We illustrate this point by discussing scrambling, focus preposing, and topicalization. The position entertained here implies that syntax is not very informative when one wants to narrow down the interpretation of terms such as “focus”, “topic”, etc

Promoting workplace-based training to fight youth unemployment in three EU countries: different strategies, different results?

During the economic crisis, youth unemployment grew exponentially in many European countries. It was argued that countries with a high level of firm involvement in the provision of initial vocational training were better equipped to address this problem. Boosting workplace‐based training was therefore seen as the right strategy to tackle unemployment. Using Denmark, Spain and the UK as case studies, this article analyses how countries with different skill formation systems have improved this type of training. While the UK reinforced the voluntaristic character of its training regime, Denmark improved the quality of its vocational education, and Spain made reforms to the training and apprenticeship contract. Interestingly, the countries achieved different results. To explain this divergence, it is argued that while the reforms made in the UK and Denmark were compatible with the national institutions and coordination mechanisms, this was not the case in Spain, where reforms were implemented in a non‐complementary way.info:eu-repo/semantics/acceptedVersio